Content area
Full text
Introduction
Liver cancer is a globally prevalent and aggressive cancer with poor prognosis (1). Examples include hepatocellular carcinoma (HCC) and hepatoblastoma (HB): HCC is estimated to be the second leading cause of cancer-associated mortality in males and the sixth in females worldwide (2), whereas HB is the most common pediatric liver tumor in the US (3,4). Currently approved therapeutic drugs for liver cancer are ineffective and result in poor patient outcomes (5). Sorafenib is a systemic drug used as a first line therapy for advanced HCC and prolongs the overall survival of patients with HCC from 7.9 to 10.7 months (6). Recent studies have indicated that sorafenib can also induce apoptosis in HB cells and inhibit the progression of HB (7,8). Sorafenib is a small molecule multiple tyrosine kinase inhibitor that can induce apoptosis in cancer cells via the downregulation of vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor receptor β (PDGFRβ), KIT proto-oncogene receptor tyrosine kinase and fms like tyrosine kinase 3 expression levels, as well as through the inhibition of the mitogen-activated protein kinase (MAPK) and Wnt/β-catenin signaling pathways (9,10). However, not all patients with liver cancer benefit from sorafenib therapy and drug resistance is often acquired within 6 month (11).
MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules consisting of 20–22 nucleotides (12). Accumulating evidence has demonstrated that miRNAs have an important role in regulating the growth of various tumors, including those in HCC and HB (13–17). Several studies have reported the important physiological role of miRNA-378a (miR-378a). Chen et al (18) reported that miR-378a inhibited prostate cancer via downregulating the MAPK1 signaling pathway. Wei et al (19) demonstrated that miR-378a promotes myoblastic differentiation by regulating histone deacetylase 4 in skeletal muscle development and Zhang et al (20) indicated that miR-378a activated the pyruvate-phosphoenolpyruvate futile cycle and regulated lipolysis. To the best of the authors' knowledge, the effects of miR-378a alone and in combination with sorafenib in HCC and HB treatment has not yet been studied.
The present study analyzed expression levels of miR-378a in liver tissue samples from healthy donors and patients with liver cancer. The effects of miR-378a alone or in combination with sorafenib therapy on the proliferation and invasion capacities of the HepG2 HB cell...